pharmachologic effect
Pharmacodynamics
Dihydrotachysterol is a provitamin D3, similar in structure to vitamin D2. When the function of the parathyroid glands is depressed, the drug increases the absorption of calcium in the intestine and increases the concentration of this trace element in the blood. The drug reduces the activity of alkaline phosphatase, preventing the development of osteoporosis. Dihydrotachysterol is characterized by a weak antirachitic effect.
An increase in the permeability of the intestinal mucosa for calcium and phosphorus ions ensures their accumulation in bone tissue. Dihydrotachysterol also takes part in the process of phosphate reabsorption in the renal tubules.
The drug can be used in long courses of treatment: it is not addictive, and cases of overdose are rarely reported. The result of the action of the active component becomes noticeable quite quickly (from several days to 1-2 weeks). However, the duration of exposure of the body to dihydrotachysterol is shorter than with vitamin D, so the risk of developing hypercalcemia will be minimal. After completing the course of therapy, the effect of using the drug lasts up to 9 weeks. Toxic effects occur when taking the drug at a dose of 25 mg per day or more and is expressed in the appearance of symptoms of hypercalcemia.
Pharmacokinetics
After oral administration on an empty stomach, up to 90% of dihydrotachysterol is absorbed from the gastrointestinal tract. The compound undergoes biotransformation in the liver, forming the active metabolite 25-hydroxyhydrotachysterol, which circulates in the blood and is resistant to further oxidation. The drug does not cause tolerance and penetrates the placental barrier and into breast milk.
The maximum therapeutic effect is observed 8 hours after the start of administration. Dihydrotachysterol is metabolized in the liver and excreted in urine, bile and feces. The half-life is 10.5–13 hours.
Application in oncology
Recent studies have proven the ability of vitamin D to fight cancer cells. But this property is inherent only in active metabolites (for example, D4), which can stimulate the growth of white blood cells and the building blocks of the immune system. Back in 2006, scientists first proved the correlation between cancer and the level of vitamin D (in the form of D4) in the patient's body. Conclusion of scientific experience: if you increase the daily norm of D-substance in the body by 1000 IU, the risk of cancer is significantly reduced. In particular, we are talking about cancer problems in the mammary gland, intestines, and ovaries. But scientific tests continue. It is possible that humanity will soon learn about new, as yet unknown properties of calciferol.
Side effects
During therapy, the following side effects may develop:
- Urinary system: with prolonged treatment - functional disorders of the kidneys;
- Cardiovascular system: heartbeat; rarely - heart rhythm disturbances;
- Digestive system: diarrhea, anorexia, vomiting, nausea; when taken in high doses – biliary dyskinesia;
- Metabolism: tissue calcification, thirst;
- Other: headache, pale skin.
Overdose
Signs of an acute overdose of Dihydrotachysterol are cylindruria, leukocyturia, proteinuria, headache, fever, hypercalcemia, arrhythmia. A chronic overdose of the drug can be suspected by such signs as calcium deposits in the intestines, kidneys, heart, blood vessels, pathological demineralization of bones, anorexia.
During a hypercalcemic crisis, a 0.9% sodium chloride solution is administered intravenously, to which loop diuretics (furosemide or ethacrynic acid) are added. Dialysis is also indicated.
special instructions
According to the instructions, Dihydrotachysterol should be taken with caution in patients with urolithiasis.
Concomitant use of other D vitamins, parathyroid drugs and calcium supplements is not recommended.
Patients with allergic reactions to nuts (including groundnut allergy) should not take the drug.
When used simultaneously with thyroid hormone replacement therapy, it may be necessary to adjust the dosage regimen of Dihydrotachysterol.
Instructions:
Clinical and pharmacological group
16.014 (Drug that regulates calcium and phosphorus metabolism)
pharmachologic effect
Regulator of calcium and phosphorus metabolism. Its chemical structure is similar to ergocalciferol (vitamin D2). Increases the permeability of the intestinal epithelium to calcium and phosphorus. Regulates the mineralization of bone tissue, as well as the process of mobilization of calcium from bone tissue. Increases the excretion of inorganic phosphates by the kidneys.
Pharmacokinetics
Dihydrotachysterol is metabolized in the liver by hydroxylation to form the active metabolite 25-hydroxydihydrotachysterol.
Dosage
When taken orally, the daily dose is 0.25-1.5 mg. The frequency of use depends on the indications and concentrations of calcium in the blood and urine.
Drug interactions
When used simultaneously with thiazide diuretics, the risk of developing hypercalcemia increases; with cholestyramine - possible disruption of the absorption of dihydrotachysterol; with barbiturates, anticonvulsants, rifampicin, isoniazid - the effectiveness of dihydrotachysterol may be reduced.
With the use of thyroid hormones, it is possible to increase the clearance of dihydrotachysterol.
Hypercalcemia caused by increased doses of dihydrotachysterol may enhance the toxic effects of cardiac glycosides.
Use during pregnancy and lactation
If use during pregnancy is necessary, the expected benefits of treatment for the mother and the potential risk to the fetus should be carefully weighed.
Dihydrotachysterol is excreted in breast milk and may cause hypercalcemia in the nursing infant.
Side effects
Adverse reactions are mainly due to hypercalcemia.
From the digestive system: anorexia, nausea, vomiting, diarrhea; when used in high doses - biliary dyskinesia.
From the cardiovascular system: palpitations; rarely - heart rhythm disturbances.
Metabolism: thirst, tissue calcification.
From the urinary system: with long-term therapy - impaired renal function.
Other: pale skin, headache.
Indications
Hypoparathyroidism (idiopathic and postoperative), pseudohypoparathyroidism, tetany (muscle cramps caused by hypocalcemia), bone diseases caused by vitamin D deficiency.
Contraindications
Hypercalcemia, hypervitaminosis D, hypersensitivity to dihydrotachysterol and other vitamin D preparations.
special instructions
Use with caution in patients with urolithiasis.
Concomitant use with other D vitamins, calcium supplements, and parathyroid drugs is not recommended.
Dihydrotachysterol should not be used in patients with allergic reactions to nuts (including groundnuts).
When used during thyroid hormone replacement therapy, adjustment of the dosage regimen of dihydrotachysterol may be required.
Drug interactions
When certain medications are used together, undesirable effects may occur:
- Cardiac glycosides and calcium antagonists: their effect may be enhanced (their doses may need to be reduced);
- Rifampicin, thiazide diuretics, vitamin D, as well as calcium-containing drugs and nutritional supplements: hypercalcemia may develop;
- Vaseline oil, barbiturates (phenobarbital), anion exchange resins (colestipol, cholestyramine), antiepileptic drugs (carbamazepine (finlepsin), phenytoin (difenin), primidone (hexamidine)): the effect of dihydrotachysterol may be weakened.
When used simultaneously with thyroxine, hypercalcemia may develop after its withdrawal.
Dihydrotachysterol
Treatment should be carried out under the control of Ca2+ and phosphorus levels in the blood (before treatment, 5-7 days from the start of treatment and then 1-2 times a month).
It is recommended to follow a diet high in Ca2+ and low in phosphorus.
When prescribed during pregnancy, the development of premature ossification in the fetus is possible.
The effect of the drug can last up to a month after its discontinuation.
1 mg of the drug is equivalent to 3 mg (120 thousand IU) of ergocalciferol.
In high doses it has a teratogenic effect.
In renal osteodystrophy with hyperphosphatemia, there is a high risk of metastatic calcification, so vitamin D is prescribed only when the concentration of phosphates in the blood is normalized.
Due to the short T1/2, overdose symptoms can be corrected more easily than when taking vitamin D analogues with a long T1/2.
Since the drug has a narrow therapeutic range, the blood concentrations of Ca2+, phosphates, creatinine, urea nitrogen, and alkaline phosphatase activity should be determined first once a week, then periodically throughout the entire period of taking the drug in therapeutic doses. The Ca2+/creatinine index is recommended to be determined every 1-3 months until the patient’s condition is stabilized. The concentration of Ca2+ in the blood should not exceed 8.8-10.3 mg/100 ml. The product of Ca2+ concentration and phosphate concentration (Ca x P) should not exceed 60 mg/dl.
Every 3-6 months (more often in case of familial hypophosphatemia, hypoparathyroidism), an X-ray examination of the skeletal system should be performed.
It should be borne in mind that sensitivity to vitamin D varies from patient to patient, and even therapeutic doses can cause hypervitaminosis.
To prevent hypovitaminosis D, a balanced diet is most preferable.
Breastfed newborns, especially those of mothers with dark skin and/or insufficient sun exposure, are at high risk of vitamin D deficiency. Newborns' sensitivity to vitamin D varies, and some may be sensitive to even very low doses. Children who receive vitamin D over a long period of time have an increased risk of stunted growth.
Maternal hypercalcemia (associated with prolonged overdose of vitamin D during pregnancy) can cause increased sensitivity to vitamin D in the fetus, suppression of parathyroid function, specific elf-like appearance syndrome, mental retardation, and aortic stenosis.
In old age, the need for vitamin D may increase due to a decrease in the absorption of vitamin D, a decrease in the skin's ability to synthesize provitamin D3, a decrease in sun exposure, and an increase in the incidence of renal failure.
Reviews of Dihydrotachysterol
According to reviews, Dihydrotachysterol is prescribed to patients with hypoparathyroidism, accompanied by a reduced rate of calcium absorption in the intestine. In this case, monotherapy with calcium preparations does not allow achieving its required concentration in the blood. It is advisable to prescribe vitamin D in the form of Dihydrotachysterol, which promotes the absorption and absorption of calcium.
The drug increases the permeability of the intestinal mucosa to calcium and increases the rate of excretion of phosphates through the kidneys. However, patients with hypoparathyroidism should take Dihydrotachysterol regularly. The drug is very effective and allows you to eliminate symptoms such as cramps, numbness of the face, and muscle pain. However, it is taken only as prescribed by a doctor and with constant monitoring of calcium levels in the blood.
Sources
If a person is able to synthesize D3 in the skin from 7-dehydrocholesterol, which is produced by most vertebrates, then the sources of D2 and D4 are mainly plants and fungi. But the best and safest way to enrich with calciferol is its own synthesis in the sun. Doctors recommend exposing your hands and face to direct rays for 10-15 minutes every day. Half-hour sunbathing helps synthesize almost 10,000 IU of vitamin D in the body. To get a similar dose of this substance from food, you need to drink 25 glasses of milk.
However, we should not forget that the main thing in any procedure is moderation, and this rule also applies to sunbathing.
Meanwhile, the ability to synthesize vitamin D depends on various factors:
- person's age;
- genetic background;
- latitude of residence;
- working conditions;
- weight and height;
- skin color.
For this reason, in some cases, doctors prescribe additional use of calciferol. Typically, pharmaceutical analogues of natural vitamins are used for this purpose.
During the winter months there is a risk of decreased calciferol synthesis as a result of decreased solar activity. This is why it is so important to find the right food sources rich in vitamin D during cold weather.
Among the most useful and rich in vitamins D2 and D4 are some types of mushrooms, especially those grown under additional ultraviolet treatment. In particular, this applies to different types of champignons, cherries, saffron milk caps, and chanterelles. There are also impressive reserves of D4 in yeast and oysters.
